Terapia antitrombotica dopo stenting nel paziente in terapia anticoagulante orale

Andrea Rubboli

Unità Operativa di Cardiologia & Laboratorio di EmodinamicaOspedale Maggiore, Bologna

Key points:1. triplice terapia è il trattamento antitrombotico ottimale2. triplice terapia è associata ad aumentato rischio emorragico3. impianto di stent  medicati da evitare/limitare

p<0.05 p=NS p<0.05 p<0.05 p=NS

(%)

Rubboli A et al. Cardiology 2005;104:101-6

Meta-analysis of ISAR, STARS, FANTASTIC e MATTIS (total pts. 2436)

TAO(+ ASA) e stent coronarico

CAPTA study

200 pts. with mechanical aortic valve

no adjunctive risk factors

ASA 100 mg + Clopidogrel 75 mg vs. OAC (INR 2.5-3.5)

Schlitt A et al. Thromb Res 2003; 109:131-5

Trombosi di protesi: 9.1 vs 0%Trombosi di protesi: 9.1 vs 0%

ACTIVE W study

6706 pts. with atrial fibrillation

≥ 1 risk factors

ASA 75-100 mg + Clopidogrel 75 mg vs. OAC (INR 2.0-3.0)

The ACTIVE Investigators. Lancet 2006; 367:1903-12

Valve thrombosis: 9.1 vs 0%

ASA + clopidogrel quando indicata TAO

+

Armstrong PW & Welsh RC, Edmonton, CDN

Bassand JP, Besançon, FRA

Bates ER, Ann Arbor, MI, USA

Belardi J, Buenos Aires, ARG

Bourassa MG & Farah B, Montrel, CDN

Chevalier B, Saint Denis, FRA

Danchin N, Paris, FRA

Di Mario C, London, GB

Eeckhout E, Lausanne, CH

Grip L, Göteborg, SWE

Grube E, Siegburg, GER

Kleiman NS, Houston, TX, USA

Meier B, Berne, CH

Morice M-C, Paris, FRA

Neumann F-J, Bad Krozingen, GER

Popma JJ, Boston, MA, USA

Rutsch W, Berlin, GER

Sanborn TA, New York, NY, USA

Schömig A, Munich, GER

Serruys PW, Rotterdam, NL

Sigwart U & Camenzind E, Geneve, CH

Sousa EMR, Sao Paulo, BRA

Urban P, Geneve, CH

Verheugt FWA, Nijmegen, NL

All casesSelected

casesNo cases

OAC + ASA 1 (4%) 5 (21%) 18 (75%)

OAC + thienopyridine 2 (8%) 1 (4%) 21 (88%)

OAC + dual antiplatelet 15 (62%) 5 (21%) 4 (17%)

83%

Rubboli A et al. Ital Heart J 2004;5:851-6

Antithrombotic treatment after coronary artery stenting in patients on chronic oral anticoagulation: an international survey of current clinical practice.

ACC/AHA/SCAI 2005 guideline update for 

percutaneous coronary intervention(J Am Coll Cardiol 2006;47:216‐235)

OAC+ASA+clopidogrel

ACC/AHA/ESC 2006 guidelines for the management 

of patients with atrial fibrillation(J Am Coll Cardiol 2006;48:854‐906)

OAC+clopidogrel

Guidelines on the management of valvular 

heart disease(Eur Heart J 2007;28:230‐268)

OAC+ASA+clopidogrel

Anticoagulants in heart disease: current status 

and perspectives(Eur Heart J 2007;28:880‐913)

OAC+ASA+clopidogrel

Management of acute myocardial infarction in patients 

presenting with persistent ST‐segment elevation(Eur Heart J 2008;29:2909‐45)

OAC+ASA+clopidogrel

Raccomandazioni attuali (livello evidenza C!!)

trombosi protesi valvolare

trombembolia arteriosa

tromboembolia venosa

trombosi di stent

emorragia

Rapporto rischio/beneficio?

1. Orford JL et al. Am J Cardiol (2004)

2. Mattichak SL et al. J Interven Cardiol (2005)

3. Khurram Z et al. J Invasive Cardiol (2006)

4. Porter A et al. Catheter Cardiovasc Interv (2006)

5. Lip GYH & Karpha M. Chest (2006)

6. Karjalainen PP et al. Eur Heart J (2007)

7. DeEugenio D et al. Pharmacotherapy (2007)

8. Rubboli A et al. Coron Artery Dis (2007)

9. Nguyen MC et al. Eur Heart J (2007)

10. Wang TY et al. Am Heart J (2008)

11. Ruiz‐Nodar JM et al. J Am Coll Cardiol (2008)

12. Rogacka R et al. J Am Coll Cardiol Intv (2008)

ANDREA RUBBOLI1, JONATHAN L. HALPERIN2, K.E. JUHANI AIRAKSINEN3, MICHAEL BUERKE4, ERIC EECKHOUT5, SAUL B. FREEDMAN6, ANTHONY H. GERSHLICK7, AXEL SCHLITT4, HUNG-FAT TSE8, FREEK W.A. VERHEUGT9 & GREGORY Y.H. LIP10

Ann Med 2008;40:428-36

Rubboli A et al. Ann Med 2008;40:428-36

Triplice terapia con TAO, ASA & tienopiridine vs. altri regimi:

meno stroke &

più emorragie (maggiori)(quanto più la terapia si prolunga)

2.26% DES vs 1.19% BMS p = 0.03

Ruiz-Nodar JM et al. Eur Heart J 2009;30:932-9

Gilard M et al. Am J Cardiol 2009;104:338-42

p = 0.2                     p = 0.04                   p = 0.3

% major bleeding

% patientsw

ithbleeding

p<0.001 p=0.64 p<0.0001

Early and late increased bleeding rates after angioplasty and stenting due tocombined antiplatelet and anticoagulant therapyChristophe Hälg, MD; Hans Peter Brunner‐La Rocca, MD;  Christoph Kaiser, MD;  Raban Jeger, MD;  Stefan Osswald, MD;  MatthiasPfisterer, MD;  Andreas Hoffmann*, MD;  for the BASKET investigators

da Eurointervention 2009;5:425-31

…. what proportion of these major hemorrhagicevents can actually be attributed to triple therapy?In other words, might triple therapy be safer than itappears?

Rubboli A & Halperin JL. Thromb Haemost 2008;100:752-3

Variabile RR 95% IC Autori

Uso di inibitori GP IIb/IIIa 5.1  1.3‐20.6 Lahtela H et al.Thromb Haemost 2009; 102:1227‐33

Approccio radiale vs. femorale 0.27 0.16‐0.45 Jolly SS et al. Am Heart J 2009; 157:132‐40

Anticoagulazione “bridge” 3.9 1.0‐15.3 Karjalainen PP et al. Eur Heart J 2008; 29:1001‐10

emorragie precoci

ANDREA RUBBOLI, M.D.,1 MAURO COLLETTA, M.D.,1 JOSE’ VALENCIA, M.D.,2 ALESSANDRO CAPECCHI, M.D.,3 NICOLETTA FRANCO, M.D.,4

LUISA ZANOLLA, M.D.,5 LUIGI LA VECCHIA, M.D.,6 GIANCARLO PIOVACCARI, M.D.,4 and GIUSEPPE DI PASQUALE, M.D.,1 for the WARfarin and coronary STENTing (WAR-STENT) Study Group

Rubboli A et al. J Interv Cardiol 2009;22:390-7

Ospedale degli Infermi, Rimini, ITA

(N Franco, G Piovaccari)

Coordinating Center

Ospedale Maggiore, Bologna, ITA

(A Rubboli, M Colletta, G Di Pasquale)

Ospedale Civile, Bentivoglio, ITA

(A Capecchi, LG Pancaldi)

Ospedale S. Bortolo, Vicenza, ITA

(L La Vecchia, A Fontanelli)

Hospital Universitario, Alicante, ESP

(J Valencia)

(%)

Rubboli A et al. J Interv Cardiol 2009;22:390-7

Author Design N° Comparison

Orford JL et al. (2004) Retrospective, 1‐center 66 none

Mattichak SL et al. (2005) Retrospective, 1‐center 82 pts. receiving ASA+clop

Khurram Z et al. (2006) Retrospective, 1‐center 214 pts. receiving ASA+clop

Porter A et al. (2006) Retrospective, 1‐center 180 none

Lip GYH & Karpha M (2006) Retrospective, 1‐center 35 within population

Karjalainen PP et al. (2007) Retrospective, multi‐center 239 pts. receiving ASA+clop

DeEugenio D et al. (2007) Retrospective, 1‐center 97 pts. receiving ASA+clop

Rubboli A et al. (2007) Retrospective, 1‐center 49 within population

Nguyen MC et al. (2007) Prospective, multi‐center (post‐hoc) 800 within population

Wang TY et al. (2008) Prospective, multi‐center (post‐hoc) 1247 within population

Ruiz‐Nodar JM et al. (2008) Retrospective, 2‐center 426 within population

Rogacka R et al. (2008) Retrospective, 2‐center 127 none

Rubboli A et al. Ann Med 2008;40:428-36

2.26% DES vs 1.19% BMS p = 0.03

Ruiz-Nodar JM et al. Eur Heart J 2009;30:932-9

only ~ 50% pts. discharged on TT

TT duration?

TT ongoing @ bleeding?

% patientsw

ithbleeding

p<0.001 p=0.64 p<0.0001

from Hälg C et al. Eurointervention 2009;5:425-31

Rubboli A et al. Eurointervention 2010; 5:105

Rossini R et al. Am J Cardiol 2008;102:1618-23

FINLAND

1. University Hospital, Turku(KE Juhani Airaksinen, MD, FESC)

2. University Hospital, Helsinki3. University Hospital, Oulu4. Central Hospital, Satakunta5. University Hospital, Kuopio6. Central Hospital, Lappi7. Central Hospital, Keski‐Suomen8. University Hospital, Tampere9. Central Hospital, Keski‐Pohjanmaa

ITALY

1. Maggiore Hospital, Bologna(Andrea Rubboli, MD, FESC)

2. S. Bortolo Hospital, Vicenza

GERMANY

1. Martin Luther University, Halle‐Wittenberg(Axel Schlitt, MD)

2. Herzzentrum, Leipzig3. Universitätklinikum, Münster4. Heart Center, Kerckhoff

GREAT BRITAIN

1. City Hospital, Birmingham

SPAIN

1. University Hospital, Alicante

A. F. C. A. S.

Management of patients withAtrial Fibrillation undergoing

Coronary Artery Stenting: a multicenter, prospective registry

Thromb & Haemost 2010;103:13-28

Triplice terapia (TAO + ASA + clopidogrel):

1. indicata nei pz. a rischio TE medio‐elevato dopo impianto di stent

2. (verosimilmente) associata ad aumentato rischio emorragico

3. da condurre con INR ai limiti inferiori del range terapeutico

4. da protrarre per il più breve tempo possibile , e quindi no stent medicati

CYPHER® TAXUS® ENDEAVOR XIENCE V

Photos on file at Abbott Vascular.

F-up Clopidogrel= 2 months

Pts Clopidogrel> 2 months

Pts

30 days 97.71% (97.71 - 99.14) 171 99.69% (99.69 - 99.96) 324

6 months 97.71% (97.71 - 99.14) 147 97.47% (97.47 - 98.73) 251

12 months 96.94% (96.94 - 98.73) 95 97.02% (97.02 - 98.45) 146

Stent ThrombosisAcute 0.2%

Sub‐acute 0%Late 0% MATRIX Registry (12-month interim analysis)

Piscione F et al. GISE 2008/TCT 2008/JIM 2009

Karjalainen PP et al. Eur Heart J 2007;28:726-32

Sørensen R et al. Lancet 2009;375:1967-74